Basement membranes are thin sheets of extracellular matrix surrounding most tissues and provide scaffolding for cells, filter proteins in tissues, and regulate cell growth and differentiation. Basement membranes consist of a unique set of proteins, including collagen IV, laminin, perlecan and nidogen/entactin. The alpha1(IV) and alpha2(IV) genes are separated by only 130 bp in a head-to-head orientation. Two enhancers, E-A and E-B were identified. E-A activated the promoter activity of both alpha1(IV) and alpha2(IV) genes, whereas E-B activated only alpha1(IV) promoter. A DNA binding protein was identified by cDNA cloning which bound to the bidirectional promoter. This protein is likely the large subunit of DNA replication complex A1 suggesting a dual function of the protein for DNA replication and transcription of collagen IV genes. Laminin is a family of heteromeric glycoproteins specific in basement membranes. A short unique sequence necessary for trimer assembly was identified at the C-terminal portion of the long arm of each of the laminin chains. An in vitro reconstitution assay using recombinant laminin chains revealed that only certain combinations of laminin chains were capable of forming trimers and dimers. Charged amino acid residues within the assembly sites of each of the chains were found to be critically important for chain-specific assembly suggesting that interchain ionic interactions determine laminin chain recognition. Thermal stability of these trimers and dimers were analyzed by CD spectroscopy. The inhibition of tumor cell metastasis by the laminin B1 chain YIGSR peptide was found to be increased by multimerization of the peptide through lysine conjugation. Nine new cell adhesion sites were identified in the G domain of the laminin A chain by a synthetic peptide approach.